Action Points

Parathyroid biopsies accounting for less than half of a parathyroid gland are not sensitive enough to reliably rule out a hyperfunctional parathyroid gland using a gamma radioactive probe after preoperative 99mTc-sestamibi injection.

Be aware, however, that manipulation and excision of half of one or more parathyroid glands may increase the patient's risk for developing hypoparathyroidism.

At least half of a suspicious gland must be biopsied during radioguided parathyroidectomy for it to be adequately evaluated for hyperfunctionality, according to a small retrospective analysis of surgical data.

When half or more of a gland was removed, it could be assessed by gamma probe with 96.6% accuracy (95% CI 91.7%-100%), reported Brendan Stack Jr., MD, of the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

If only one-quarter to one-half of a gland was biopsied, the accuracy fell to 87% (95% CI 79.3%-94.7%), and if less than one-quarter was excised, the accuracy was only 63.6% (95% CI 54.5%-72.8%), according to the study, online in JAMA Otolaryngology–Head & Neck Surgery.

"To our knowledge, this is the first study to investigate the amount of a parathyroid gland that must be resected to reliably identify a hyperfunctional lesion by the Norman 20% rule," Stack and colleagues wrote. "Parathyroid biopsies accounting for less than half of a parathyroid gland are not sensitive enough to reliably rule out a hyperfunctional parathyroid gland.

"If performed, pie-shaped biopsies originating from the center of the gland are associated with a lower rate of false-negative results compared with peripheral biopsies of the same size. However, manipulation and excision of half of one or more parathyroid glands for ex vivo counts may increase the patient's risk for developing hypoparathyroidism."

The researchers retrospectively analyzed data from 253 biopsy specimens obtained from 33 parathyroid glands (18 solitary adenomas, 10 double adenomas, four cases of hyperplasia, and one specimen that was normal). The glands were surgically removed from 24 patients who consecutively underwent surgery for primary hyperparathyroidism from May to October 2015 at a tertiary academic medical center. The patients' mean age was 67; 16 were women, and eight were men.

The patients were injected with 99mTc-labeled sestamibi (18.4-30.0 mCi) 1 to 5 hours prior to starting the procedure. A hand-held gamma probe (neo2000GDS; Neoprobe Corp) was used to evaluate the biopsy specimens, utilizing the Norman 20% rule, which states that a hyperfunctional sample will contain more than 20% of the background radiation.

In addition, intraoperative parathyroid hormone level changes were measured preoperatively and at two different time points (10 minutes and 20 minutes) following excision of the final diseased gland.

The study also assessed whether the shape of the biopsy specimen affected the accuracy of its analysis by gamma probe. When the investigators compared 39 pie-shaped and 86 parallel/vertical biopsies of equal weight, no significant difference in satisfaction was found related to the 20% rule between biopsy techniques if at least a quarter of the gland was removed (94.9% versus 88.4%; absolute difference, 6.5%; 95% CI -3.0% to 16.0%).

However, when less than a quarter of the gland was removed, pie-shaped biopsies were more likely to satisfy the 20% rule compared with parallel biopsies of the same weight (78.4% versus 56.2%; absolute difference, 22.2%; 95% CI 4.7%-39.7%), the investigators said.

The study found no differences between biopsy samples from single adenomas versus double adenomas when comparing the radioactivity (normalized to background) per milligram of parathyroid tissue. However, adenomas contained considerably higher radioactivity compared with hyperplastic and normal glands.

Regarding study limitations, Stack et al noted the small number of patients and the lack of normal parathyroid glands available for comparison, since these are not usually biopsied unless there is considerable suspicion that the gland is hyperfunctional. "While parathyroid gland weight and size have been intensively examined for their relationship to ex vivo parathyroid counts, no studies have quantified the minimal proportion of individual parathyroid glands that must be biopsied to make a reliable intraoperative radioguided determination of normal versus hyperfunctional tissue.

"This is especially important when the gamma probe is used as the sole determinant of parathyroid function and serves as the deciding factor for whether a parathyroid gland is removed or left in situ," the investigators said.

Click here for the American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons' position statement on diagnosing and managing primary hyperparathyroidism.

The authors reported that they have no potential conflicts of interest.